Metastasis to the liver is a common event in clinicaloncology. Blood-borne tumor cells (TCs) arriving to the coined the term metastasis in 1829 in his treatise ''Reliver sinusoids run into a special vascular bed. The lining cherches du Cancer,'' the metastatic cascade has been of liver sinusoids is shared by Kupffer cells (KCs) and exhaustively studied.1,2 Metastases originate from a seendothelial cells. KCs, liver-fixed macrophages, are re-lective population of cells within the great biological sponsible for detection and removal of ''non-self'' parti-heterogeneity of the tumor.3 They must invade the vascles. To investigate their role in arresting blood-borne cular wall to be dislodged into the circulation and surTCs and controlling tumor growth, we injected a synge-vive in the blood stream until they arrest at the distant neic colon carcinoma cell line into a mesenteric vein of vascular bed of the target organ by adherence or metwo groups of rats; one group was without Kupffer cells chanical trapping. Then, they have to proliferate to iniand the other normal controls. We removed the liver of tiate a metastatic colony. these animals at different time intervals and performedLiver metastasis is a common event in cancer paimmunohistochemical analysis with monoclonal antitients. This is of particular relevance for neoplasias of bodies (MoAbs) against our tumor cell line, three macrophage subpopulations, natural killer cells, and B and T the gastrointestinal tract, because the liver is the first lymphocytes. Additionally, we showed in vitro spontane-vascular bed to be encountered by blood-borne tumor ous cytotoxicity of KCs against our tumor cell line. Re-cells (TCs) through the portal system. 4 The lumen of sults suggest that KCs play a relevant role in arresting liver sinusoids differ from the ordinary capillaries in circulating TCs at the liver sinusoid, although it is lim-that, besides endothelial cells, the stellate cells of von ited to a small number of malignant cells. They also seem Kupffer are lining the sinusoid wall.5 Kupffer cells to play a major role in clearing neoplastic cells from the (KCs) represent one of the largest populations of the liver parenchyma, in controlling tumor growth in the mononuclear phagocyte system in the body. Their privery early stages of metastatic development, and in mod-mary function is to discriminate between ''self'' and ulating the host immune response to cancer cells. (HEPA-''non-self'' particles, playing a prominent role as anti-

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The rat monoclonal antibody LMR-12 was shown earlier to react with a plasma membrane protein, upregulated in multidrugresistant cell lines. In this study, we observed distinct LMR-12 staining in 36 out of 55 non-drug-selected tumour cell lines, including melanomas, renal cell-, colon-and lung carcinomas, whereas in other tumour types, such as leukaemia and ovarian cancer, LMR-12 staining was generally low or absent. The cDNA encoding the LMR-12 antigen was isolated from a library of the multidrug-resistant human fibrosarcoma cell line HT1080/DR4 by expression cloning in MOP8 cells. Sequence analysis showed that the LMR-12 antigen is identical to the major histocompatibility complex class I molecule beta 2-microglobulin (b 2 -m). The LMR-12/ b 2 -m staining results were confirmed by mRNA microarray data from an independent National Cancer Institute study, as well as by newly obtained reverse transcriptase polymerase chain reaction data. Further analysis of the microarray data showed that b 2 -m levels closely reflected levels of major histocompatibility complex class I heavy chains and the transporter associated with antigen processing. Since the ABC transporter associated with antigen processing was previously shown to contribute to multidrug-resistance, it may very well be that the observed LMR-12/ b 2 -m levels are secondary to (elevated) levels of the transporter associated with antigen processing. A perspective arising from the present study is that drug resistant tumour cells may, by having elevated levels of major histocompatibility complex related molecules, be particular good candidates for alternative therapeutic therapies, such as cytotoxic T cell mediated immune-therapies.

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